Griffith David E, Daley Charles L
Division of Mycobacterial and Respiratory Infections, Department of Medicine, National Jewish Health, Denver, CO.
Division of Mycobacterial and Respiratory Infections, Department of Medicine, National Jewish Health, Denver, CO.
Chest. 2022 Jan;161(1):64-75. doi: 10.1016/j.chest.2021.07.035. Epub 2021 Jul 24.
Mycobacterium abscessus is the second most common nontuberculous mycobacterial lung disease pathogen and comprises three subspecies: abscessus, massiliense, and bolletii. Subspecies identification is critical for disease management, as subspecies abscessus and bolletii have an inducible macrolide resistance gene [erm(41)] that results in clinical macrolide resistance. In contrast, subspecies massiliense does not have an active erm(41) gene and is therefore susceptible in vitro and clinically to macrolide-containing regimens. M abscessus is also vulnerable to acquired mutational macrolide resistance. Macrolide resistance has such a profoundly negative impact on M abscessus treatment response that preserving macrolide susceptibility with adequate companion drugs for macrolides is among the highest treatment priorities. After the macrolides, amikacin is regarded as the next most important drug for M abscessus treatment, although data validating that assertion are lacking. The considerations for preventing acquired macrolide resistance also apply to amikacin. Recent guidelines suggest that treatment should be guided by in vitro susceptibilities but, aside from macrolides and amikacin, no other antibiotics have a validated minimum inhibitory concentration for M abscessus. Currently, phase therapy (intensive and continuation) is recommended for M abscessus. This approach is successful with macrolide-susceptible M abscessus but not with macrolide-resistant M abscessus, in which even more aggressive therapy is not predictably successful. Newer drugs have become available, with encouraging in vitro activity against M abscessus, but in vivo validation of their superiority to current agents is not yet available. In the absence of unequivocally effective regimens, we offer suggestions for managing this treatment-refractory organism.
脓肿分枝杆菌是第二常见的非结核分枝杆菌肺病病原体，包括三个亚种：脓肿亚种、马赛亚种和博勒亚种。亚种鉴定对疾病管理至关重要，因为脓肿亚种和博勒亚种具有可诱导的大环内酯耐药基因[erm(41)]，导致临床大环内酯耐药。相比之下，马赛亚种没有活性erm(41)基因，因此在体外和临床上对含大环内酯的治疗方案敏感。脓肿分枝杆菌也易发生获得性大环内酯耐药突变。大环内酯耐药对脓肿分枝杆菌的治疗反应有极其负面的影响，因此使用适当的大环内酯类联合药物保持大环内酯敏感性是最高治疗优先事项之一。在大环内酯类药物之后，阿米卡星被认为是治疗脓肿分枝杆菌的第二重要药物，尽管缺乏验证这一说法的数据。预防获得性大环内酯耐药的考虑因素也适用于阿米卡星。最近的指南建议治疗应根据体外药敏试验进行指导，但除了大环内酯类和阿米卡星外，没有其他抗生素对脓肿分枝杆菌有经过验证的最低抑菌浓度。目前，推荐对脓肿分枝杆菌采用阶段治疗（强化期和延续期）。这种方法对大环内酯敏感的脓肿分枝杆菌治疗成功，但对大环内酯耐药的脓肿分枝杆菌则不然，在后者中，即使更积极的治疗也不一定成功。已有新型药物问世，其对脓肿分枝杆菌的体外活性令人鼓舞，但尚未在体内验证其优于现有药物。在缺乏明确有效的治疗方案的情况下，我们为管理这种难治性病原体提供建议。
